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Diseases / List of Viral Diseases / Disease description:

Lymphocytic Choriomeningitis

INDEX - INFORMATION AVAILABLE

GENERAL INFORMATION

SUSCEPTIBILITY, DISEASE CHARACTERISTICS & DIAGNOSIS

TREATMENT & CONTROL

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THE FOLLOWING INFORMATION IS HELD ON THE INFECTIOUS AGENT INFORMATION PAGE
Arenaviridae: Lymphocytic Choriomeningitis Virus (LCMV):

  • Virus Structure and Identification
  • Associated Host Species of Virus (Animal Types Affected) and Hazard / Risk
  • Virus Life Cycle, Transmission and Effects of Chemicals
  • Transmission and Biogeographical / Climatic Range for Virus

CLICK THIS LINK FOR Arenaviridae: Lymphocytic Choriomeningitis Virus (LCMV)

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General and References

Disease Summary

An arenavirus infection, carried by mice (often subclinically) and causing often fatal systemic disease, characterised by hepatitis in marmosets, tamarins and some other primates. Zoonotic.

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Alternative Names (Synonyms)

  • Callatrichid Hepatitis
  • LCMV infection

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Disease Type

 Viral

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Infectious/Non-Infectious Agent (directly associated with the Disease)

Lymphocytic Choriomeninigitis Virus (LCMV), an arenavirus. (D267.035.w35)
  • In 1989 it was shown by passage following filtration that the agent of callitrichid hepatitis (CH) was a virus smaller than 220 nm; enveloped viruslike particles 85 - 105 nm diameter were detected in the liver of infected marmosets. (J100.160.w1)
  • In 1990, CH-specific antigens were detected in livers of affected callitrichids, but not in livers of unaffected animals. (J80.64.w1)
  • In 1991, an arenavirus was isolated from a marmoset with CH and shown to be closely related to LCMV. (J80.65.w1)
  • In 1995, cDNA sequence analysis confirmed that the aetiologic agent of callitrichid hepatitis is LCMV. (J80.69.w2)

Note: marmosets and tamarins become infected by eating infected rodents; horizontal transmission between callitrichids has not been observed. (J100.167.w1)

Species/Taxa

Chemical

  • --

Physical

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References

Disease Author

Debra Bourne MA VetMB PhD MRCVS (V.w5)

Referee

Prof. Juan C. de la Torre PhD (V.w168)

References

Detailed references are provided attached to specific sections.

ORGANISATIONS-

  • --

ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

 

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Epidemiology and Host Susceptibility Factors

Incubation Period, Time Course and Persistence of Disease

Notes
1) INCUBATION PERIOD
In experimentally infected mice, incubation periods of four to 12 days are reported. In experimentally infected Callithrix jacchus - Common marmoset, Macaca fascicularis - Crab-eating macaque and Macaca mulatta - Rhesus macaque the incubation period was up to a week. In a natural outbreak following feeding with neonatal mice, the incubation periods seen were 11 - 20 days in Callithrix pygmaea - Pygmy marmosets and 8 - 9 days in Leontopithecus rosalia - Golden lion tamarins. In humans, it is usually about 5 - 13 days, but sometimes several weeks.
2) DISEASE DURATION (TO RECOVERY OR DEATH) IN INDIVIDUAL ANIMALS

Disease duration is variable from very short (affected individuals found dead) to a week or longer in fatal infection of marmosets and tamarins, with some species differences noted. In mice, generally 1 - 3 days to death, or 4 - 5 days of illness before recovery; sometimes sudden death 5 - 7 days post infection; clinical signs can continue for a few weeks following intranasal inoculation of day-old mice. In guinea pigs, 3 - 21 days to death in fatal infections. Experimentally infected Macaca mulatta - Rhesus macaque were ill for about two days then recovered, following gastric inoculation, but showed severe signs for about six days before euthanasia after intravenous inoculation. In humans, generally one to three weeks, sometimes biphasic (a few days of illness, recovery then a second period of sickness; convalescence can be prolonged.

  • In mice infected by intracranial inoculation, one to two days from first signs to death. (J494.63.w1)
  • In mice inoculated intranasally at one day old, clinical signs occurred for 3 - 4 weeks before the mice recovered. (J494.69.w1)
  • In mice inoculated intraperitoneally, clinical signs occurred for about a week before the mice recovered. (J494.63.w1)
  • In mice, generally 1 - 3 days to death, or 4 - 5 days of illness before recovery; sometimes sudden death 5 - 7 days post infection. (B558.w1)
  • In experimentally infected guinea pigs, following subcutaneous, intranasal or intracranial inoculation, clinical signs may continue for three to 21 days before death in fatal cases, and in severe non-fatal cases, a long time may be required to regain weight lost during the period of clinical signs. (J494.63.w1)
  • In Callimico goeldii - Goeldi's monkey, Callithrix argentata melanura (Callithrix argentata - Silvery marmoset), and Saguinus oedipus - Cotton-top tamarins, sudden death or death only a few hours after the development of clinical signs. (J83.16.w1)
  • In outbreaks in Leontopithecus rosalia - Golden lion tamarins in two years in one zoo, variable from sudden death to as long as 10 days from onset of illness to death. (J2.20.w6)
  • In outbreaks in tamarins and marmosets, mainly Leontopithecus rosalia - Golden lion tamarins, most cases were of acute onset and short clinical course, but some individuals had a longer illness. (J2.20.w6)
  • In Callithrix jacchus - Common marmoset following experimental inoculation, death or euthanased after one or two days from the onset of clinical signs. (J100.160.w1)
  • In Callithrix pygmaea - Pygmy marmosets at Fort Worth Zoo, 1991, following feeding with neonatal mice, 5 - 7 days after onset of clinical signs. (J100.167.w1)
  • In Leontopithecus rosalia - Golden lion tamarins at Fort Worth Zoo, 1991, following feeding with neonatal mice, 24 - 48 hours from first clinical signs to death in individuals with seizures. One individual was ill for three days then recovered, and one animal developed mild ataxia for a period of several days. (J100.167.w1)
  • In Callithrix geoffroi - Geoffroy's marmoset in the UK, 2005, acute disease. (P3.2007b.w1)
  • In cynomolgus monkeys (Macaca fascicularis - Crab-eating macaque
    • Following experimental subcutaneous inoculation with LCMV WE strain, about 6 - 7 days from first signs to death. (J214.134.w1)
    • Following natural aerosol transmission, no more than five days to death. (J214.134.w1)
  • In Macaca mulatta - Rhesus macaque and cynomolgus monkeys (Macaca fascicularis - Crab-eating macaque), LCMV WE is "rapidly fatal" following peripheral, intracranial or aerosol inoculation. (J214.134.w1)
  • In Macaca mulatta - Rhesus macaque:
    • Following gastric inoculation with LCMV WE strain, mild clinical signs for about two days before returning to normal condition. (J117.67.w1)
    • Following intravenous inoculation with LCMV WE strain, clinical signs for about six days before the animals were euthanased due to severe clinical signs. (J117.67.w1)
  • In humans, one to three weeks; recurrent episodes of illness may occur during this time. (J323.66.w1)
    • Infection may be biphasic. (J421.36.w1)
    • In one outbreak, illness lasted one day to two months, typically 5-15 days for "flu-like" illness; 25% of infections were biphasic with about 3-7 days of illness, then 3-5 days well followed by a further 3-5 days of illness, often less severe than the initial illness. (J416.232.w1)
    • In an individual with fatal infection, death occurred on the 13th day of illness. (J106.23.w1)
    • During an outbreak in 15 members of staff at a university hospital, illness lasted 1-3 weeks, often being biphasic, and was followed by prolonged convalescence. (J496.58.w1)
3) TIME COURSE / PERSISTENCE OF DISEASE IN A SUSCEPTIBLE POPULATION
This infection can persist indefinitely in a population of mice. Outbreaks in marmosets and tamarins have taken place over several weeks to several months while in an outbreak in Macaca fascicularis - Crab-eating macaque all affected animals died over five days. In humans, one outbreak associated with pet hamsters occurred over four months while in an outbreak at a university hospital, cases occurred sporadically over a period of at least two years before LCM was recognised.
  • In mice, infection may persist in the population indefinitely. (J494.69.w1)
  • In an outbreak in Callimico goeldii - Goeldi's monkey, Callithrix argentata melanura (Callithrix argentata - Silvery marmoset), and Saguinus oedipus - Cotton-top tamarins, five deaths occurred over a period of five days, followed by two weeks without any deaths, then four more deaths over 12 days, then 12 weeks after the first deaths, three deaths over a period of five days. (J83.16.w1)
  • In an outbreak in Leontopithecus rosalia - Golden lion tamarins, six of seven animals in one group died over a period of 36 days, with the final animal dying 86 days later. (P1.1982.w3)
  • In outbreaks in two years in one zoo, one group of three Leontopithecus rosalia - Golden lion tamarins died a month apart from each other, two months or so later three of another group died over a period of about nine days, and two years later three individuals from a group all became ill and were died or euthanased at the same time. (J2.20.w6)
  • At Fort Worth Zoo in 1991, illness occurred over a period of about 20 days, with one animal showing mild ataxia about three weeks later. (J100.167.w1)
  • In an outbreak in humans in New York State, associated with pet hamsters, 57 cases occurred over a period of four months. (J416.232.w1)
  • During an outbreak in members of staff at a university hospital, cases occurred sporadically over a period of at least two years before LCM was recognised. (J496.58.w1)
  • In naturally infected (aerosol) cynomolgus monkeys (Macaca fascicularis - Crab-eating macaque), all affected individuals died over a period of five days. (J214.134.w1)

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Mortality / Morbidity / Susceptibility / Life stage affected

Notes
1) NUMBER OF DEATHS

 In rodents, mortality may be as low as 2% in an infected mouse colony or as high as over 80% in guinea pigs (depending on the virus strain). During outbreaks in zoos, mortality has varied from as few as one in six of a group of Saguinus oedipus - Cotton-top tamarins to nine of ten Leontopithecus rosalia - Golden lion tamarins in three groups, with the deaths of all animals which became ill. Less than 1% of recognised infections in humans are fatal, but very high mortality rates have been seen in transplant patients after receipt of infected organs (kidney, liver or lung). In macaques, death rates may vary depending on the strain of LCMV; following aerosol infection, death rates depended on dose.

Rodents

  • In a colony of infected mice, it was estimated that at least 50% of the colony were infected but mortality was less than 2% of the infected mice. (J494.63.w1)
  • In guinea pigs infected by subcutaneous, intranasal or intracranial inoculation, variable depending on virus strain, but sometimes over 80%. (J494.63.w1)
  • In rats inoculated intracerebrally, 5/7 died. (J494.63.w1)
  • In Mesocricetus auratus - Golden Hamster, no deaths in individuals inoculated as young adults, but death of about 50% of those infected neonatally. (J267.13.w1)
  • In four rabbits experimentally inoculated by various routes including intracranial, no deaths occurred. (J494.63.w1)

Primates

2) NUMBER OF ANIMALS AFFECTED

In rodents, variable. During outbreaks in zoos, variable percentages of individuals in groups have been affected, from as few as one in six of a group of Saguinus oedipus - Cotton-top tamarins were affected but nine of ten Leontopithecus rosalia - Golden lion tamarins in three groups were affected, with the deaths of all animals which became ill. 

Rodents

  • In mice: variable. 
    • In a colony of infected mice, it was estimated that at least 50% of the colony were infected but morbidity was less than 20% of infected mice. (J494.63.w1)
    • In one colony, over a period of two months the rate of infection was nearly 100% and about 20% were clinically affected. (J494.69.w1)
  • In guinea pigs infected by subcutaneous, intranasal or intracranial inoculation, variable depending on virus strain. (J494.63.w1)
  • In rats inoculated intracerebrally, 5/7 died. (J494.63.w1)
  • In Mesocricetus auratus - Golden Hamster, development of viraemia but no illness in individuals inoculated as young adults, while in those infected neonatally all developed viraemia and viuria and about 50% showed delayed (starting at 7-42 weeks) progressive illness. (J267.13.w1)

Primates

Lagomorphs

  • In four rabbits experimentally inoculated by various routes including intracranial, fever (41.0 C) was noted in one rabbit; no other signs occurred. (J494.63.w1)
3) EFFECTS OF AGE, SEX AND REPRODUCTIVE STATUS

In mice, disease may be mild in individuals infected in utero with disease seen in those infected as young pups but not in mice infected later in life. In Mesocricetus auratus - Golden Hamster, clinical disease was seen in those infected in utero or as neonates, but not in those infected as young adults. There is no obvious relationship between disease and either age or sex in non-human primates or in humans. In rodents there are definite effects of age on severity of disease.

Rodents

  • In an infected colony of mice, this was seen as a disease of young mice, occurring in pups up to one month old. (J494.69.w1)
    • Transmission of infection from infected mice appeared to occur more readily to young mice than to older mice. (J494.69.w1)
    • Following intranasal inoculation, mice of five weeks of age or older rarely showed clinical signs, while a higher proportion of mice infected at one day or 2-3 weeks showed clinical signs. (J494.69.w1)
  • Milder disease may occur following intrauterine infection than if mice are infected after birth. (J494.69.w1)
  • In Mesocricetus auratus - Golden Hamster, infection of young adults resulted in no clinical disease but viraemia for up to three months and viruria (virus in the urine) for up to six months. In individuals infected as neonates or in utero, about half developed chronic progressive disease starting 7 - 42 weeks post infection, while the others developed higher CF antibody titres and the titres of virus in blood decreased from 12 weeks, although virus persisted longer in urine. (J267.13.w1)

Primates

  • In an outbreak in 12 Leontopithecus rosalia - Golden lion tamarins, adults and juveniles were affected; one female aborted. (P1.1982.w3)
  • In outbreaks in Leontopithecus rosalia - Golden lion tamarins from three groups in two years in one zoo, affected animals included adults and juveniles, males and females. The one unaffected animal was an adult female. (J2.20.w6)
  • In humans, may occur in children and adults. (J323.66.w1); in one outbreak associated with pet hamsters, cases occurred in individuals ranging from 3-70 years. (J416.232.w1)
4) EFFECTS OF BODY CONDITION AND OTHER DISEASES

The following factors appear to affect susceptibility to the development of clinical signs associated with LCMV: immunosuppression (increases susceptibility), genetic strain (in inbred rodents) and previous infection with a milder strain of LCMV.

  • Genetic strain affects susceptibility in inbred rodents. (J71.97.w1)
  • Immunosuppression increases susceptibility; immunosuppressed hamsters all succumbed to infection with a pathogenic strain (LCMV-WE) while non-suppressed hamsters of some strains were resistant to this infection, and some immunosuppressed hamsters succumbed to LCMV-ARM strain while this was avirulent in hamsters which were not immunosuppressed. (J71.97.w1)
  • Previous infection with LCMV resulting in mild or subclinical disease can be protective against a later challenge with LCMV which would be lethal in a naive individual of the same species. (J71.149.w1, J117.72.w1)
    • Three of four experimentally infected macaques, which developed IgG ELISA antibodies following initial infection with a non-lethal strain (LCMV-ARM) or by a non-lethal route (intragastric) later survived challenge with an intravenous inoculation of a lethal strain (LCMV-WE). Unlike the other three animals, the individual which did not survive challenge had not developed antibodies following initial infection (as indicated by IgG ELISA) and had poor cell-mediated immunity response - a low stimulation index (< 5) of lymphocytes (indicated by lymphocyte proliferation assay). (J71.149.w1, J117.72.w1)

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Clinical & Pathological Characteristics, and Diagnosis

Clinical Signs (by physiological system)

Overall Clinical Presentation
Rodents
  • In a colony of infected mice, clinical signs included: (J494.63.w1)
    • no clinical signs and a normal growth rate;
    • conjunctivitis and photophobia only;
    • emaciation, ruffled fur, drowsiness/somnolence, sitting in a corner alone, slow stiff movements, reduced growth rate with legs appearing long in proportion to the body, which was thin.
    • found dead.

    (J494.63.w1)

  • In mice infected by intracranial inoculation:
    • Initially general malaise and looking ill, quiet, sitting alone, fur often ruffled
    • If lifted by the tail, limb tremors and later spastic convulsions of the hind legs; convulsions may last for one to several minutes and may be fatal.
    • Spontaneous fatal convulsions also occur.

    (J494.63.w1)

  • In mice with acute clinical disease: (B558.w1)
    • Rough hair coat, humped posture, lethargy, blepharitis, facial oedema.
    • Sometimes spontaneous clonic convulsions.
    • If picked up by the tail and briefly twirled, convulsive seizures occur.
    • Rarely paralysis after acute disease.
    • Occasionally sudden death 5 - 7 days post infection without any other signs. (B558.w1)
    • In mice infected when older than 3 days but younger than 21 days, growth retardation, developmental alopecia, hyperexcitability and weakness may occur, with either death, recovery without persistent mental impairment or recovery but with persistent impairment. (B558.w1)
  • In guinea pigs infected by subcutaneous, intranasal or intracranial inoculation: (J494.63.w1)
    • Fever (sometime this is the only clinical sign);
    • Weight loss, sometimes severe (emaciation);
    • Laboured breathing, increasing to dyspnoea, or gradually improving;
    • In severe cases somnolence, salivation, seropurulent conjunctivitis.

    (J494.63.w1)

  • In Rattus norvegicus - Brown rat inoculated intracerebrally, clinical signs were "somewhat similar to those presented by intracerebrally injected mice" and were characterised by clonic-tonic spasms of the leg and neck muscles. (J494.63.w1)
  • In about 50% of Mesocricetus auratus - Golden Hamster following neonatal inoculation or infection in utero: (J267.13.w1)
    • Signs of illness included decreased activity and ungroomed coat, followed by weight loss, hunched posture and blepharitis, deteriorating to become moribund after several weeks to months. (J267.13.w1)
    • No signs in the other infected individuals. (J267.13.w1)
    • Reduced breeding success (reduced litter size and reduced survival to weaning) in congenitally infected hamsters. (J267.13.w1)
  • In Mesocricetus auratus - Golden Hamster infected as young adults: no clinical signs. (J267.13.w1)
Lagomorphs
  • In four rabbits experimentally inoculated by various routes including intracranially, fever (41.0 C) was noted in one rabbit on the third day post inoculation; no other signs occurred. (J494.63.w1)
Primates

In marmosets and tamarins, some animals have been found dead; others have shown combinations of weakness, anorexia, dyspnoea, incoordination/ataxia, jaundice, haemorrhages and seizures. In humans, infection may be asymptomatic, "flu-like", or produce signs of aseptic meningitis or meningoencephalitis.

  • In marmosets: dyspnoea, anorexia, lethargy, jaundice, haemorrhages. (D267.035.w35, J80.65.w1)
  • Non-specific: dyspnoea, anorexia, weakness, lethargy, often progressing to prostration and death. (J80.65.w1)
  • In an outbreak in a zoo involving Callimico goeldii - Goeldi's monkey, Callithrix argentata melanura (Callithrix argentata - Silvery marmoset), and Saguinus oedipus - Cotton-top tamarins, sudden death or collapse and apparent inability of the animal to move its legs, followed by death within a few hours. (J83.16.w1)
  • In an outbreak in 12 Leontopithecus rosalia - Golden lion tamarins (data from seven animals), clinical signs included dyspnoea, anorexia, cessation of drinking and lethargy. Affected animals lay in sternal recumbency, eyes closed. If handled, respiratory difficulties increased and the animals became cyanotic. (P1.1982.w3)
  • In outbreaks in Leontopithecus rosalia - Golden lion tamarins from three groups in two years in one zoo, signs varied from none (found dead) to found moribund, to weakness and anorexia, progressing to death (or euthanasia while moribund). (J2.20.w6)
  • In Callithrix jacchus - Common marmoset following experimental inoculation, weakness, lethargy and anorexia. (J100.160.w1)
  • In Callithrix pygmaea - Pygmy marmosets at Fort Worth Zoo, 1991, following feeding with neonatal mice, weakness, incoordination, in some animals jaundice, and death. (J100.167.w1)
  • In Leontopithecus rosalia - Golden lion tamarins at Fort Worth Zoo, 1991, following feeding with neonatal mice, weakness, anorexia and ataxia, mucus-covered faeces, and in the three fatal cases, grand mal seizures. The animal that survived developed inguinal petechiae four days after other signs had ceased. A female aborted (due to infection or ribavirin treatment) and later developed mild ataxia for several days. (J100.167.w1)
  • In Leontopithecus rosalia - Golden lion tamarin at Chafee Zoological Park, California, 1995, seizures were noted alongside other typical clinical signs. (P1.1996.w8)
  • In a Callimico goeldii - Goeldi's monkey in Dortmund Zoo, Germany, jaundice, fever, apathy and ataxia were noted before death. (J20.284.w1)
  • In one Callithrix pygmaea - Pygmy marmoset in Dortmund Zoo, Germany, jaundice was noted before death. (J20.284.w1)
  • In Colobus guereza - Black and white colobus (Cercopithecidae - Old-world monkeys (Family)) in the UK, June 2006, severe neurological signs. (P3.2007b.w1)
  • In cynomolgus monkeys (Macaca fascicularis - Crab-eating macaque) following experimental subcutaneous inoculation with LCMV WE, fever (39 - 40 C / 102 - 104 F) and anorexia developed (within seven days of infection), with cutaneous petechiae and ecchymoses from day 10 onwards, plus a blood-tinged nasal exudate. In the hours before death, body temperature "dropped precipitously". (J214.134.w1)
  • In cynomolgus monkeys (Macaca fascicularis - Crab-eating macaque) following experimental subcutaneous inoculation with LCMV ARM strain, no clinical signs. (J214.134.w1)
  •  In Macaca mulatta - Rhesus macaques:
    • Following gastric inoculation with LCMV WE, slight fever for about two days and an ungroomed appearance (coat appearing greasy and unkempt) for the same length of time. (J117.67.w1)
    • Following intravenous inoculation with LCMV WE, initially fever (reaching 105 F (41 C)) and an ungroomed appearance (coat appearing greasy and unkempt), later development of anorexia, listlessness, crouching and shivering, diarrhoea, orbital haemorrhage and hypovolaemic shock. (J117.67.w1)
  • In Macaca mulatta - Rhesus macaques, clinical signs following intragastric inoculation can vary from subclinical through disease with weight loss to rapidly fatal disease. (J117.72.w1)
  • In Macaca mulatta - Rhesus macaques following gastric or intravenous inoculation with LCMV ARM, no clinical signs. (J71.149.w1)
  • Has been associated with malignant lymphoma (in baboons and macaques). (B644.1.w1)
  • In New World monkeys, fatal malignant B-cell lymphoma has been seen following experimental infection with some lymphocryptoviruses. (B644.1.w1)
  • In humans (Homo sapiens - Human):
    • May be asymptomatic, "flu-like", or produce signs of aseptic meningitis or meningoencephalitis. (J214.133.w1)
    • Sub-clinical infection may occur. Clinical illness is usually a non-specific influenza-like syndrome, varying in severity. Meningitis or meningoencephalitis occur infrequently. (J496.58.w1)
    • Subclinical; (J83.2.w1)
    • 'flu-like illness; (J83.2.w1) 
      • Commonly fever, nausea and myalgia (muscle aches); cough, rash and diarrhoea are uncommonly reported. (J323.66.w1)
      • Commonly fever, headache, myalgia, nausea and vomiting. Less often sore throat and photophobia, rarely rash, diarrhoea, cough, enlarged lymph nodes and orchitis. (J421.36.w1) Occasionally, severe pain associated with eye movements (J421.36.w1)
      • In one outbreak associated with pet hamsters in New York State, 6% of seropositive individuals had no clinical signs, Fever was seen in 90% (37-41 C/100-106 F, usually not above 39 C/102 F), headache in 85%, myalgia in 80% pain on moving the eyes in 59%, nausea in 53% and vomiting in 35%; other signs reported included sore throat (24%), photophobia (24%), cough (18%), swollen glands (16%), diarrhoea (16%), rash (12%), upper respiratory tracts symptoms (12%), orchitis in one male (5% of males) and notable arthritis of several joints in one female. In three females aged 14-19 years, there was prolonged (2-4 weeks) intermittent fever, with adenopathy, pharyngitis, rash and extreme fatigue. (J416.232.w1)
    • Three clinical forms: (B558.w1)
      • Influenza-like, including fever, malaise, myalgia, photophobia, bronchitis and coryza with uneventful recovery after one to two weeks. (B558.w1)
      • Signs of meningitis: stiff neck, headache, confusion, nausea. This may be seen alone or after recovery from 'flu-like illness. Generally short duration but sometimes more severe and sometimes lasting two weeks or longer. (B558.w1)
      • Meningoencephalitis or meningoencephalomyelitis with signs including somnolence, paraesthesia, alteration of deep reflexes and paralyis. This form is often longer lasting and can be fatal. Survivors may continue to have headache. paralysis and personality change. Convalescence commonly involves arthralgia, sometimes prolonged.
      • Other reported signs include unilateral orchitis and mild generalised alopecia. (B558.w1)
    • In a minority of cases, following 'flu-like illness, about 7-14 days later more severe illness with signs of meningitis. (J83.2.w1) Severe headache, photophobia, stiff neck and retrobulbar pain may be present. (J323.66.w1)
    • In individuals with CNS signs, disease is often bimodal, with initial 'flu-like illness including fever, headache and myalgia, a period of remission, then fever, headache and other neurological signs. (J214.133.w1)
    • In an individual with fatal infection, headache, fever (100.4 F, rising to 103 F), developing to confusion, nuchal rigidity and other neurological signs. Death occurred on the 13th day of illness. (J106.23.w1)
    • During an outbreak in 15 members of staff at a university hospital, all showed prolonged fever (1-3 weeks), malaise and weakness, and most (12 or more) had myalgia, retro-orbital headache, rigors, photophobia, and anorexia and/or nausea. Additional symptoms included sore throat (10/15), arthralgias (9/15), listlessness and apathy (9/15), dysaesthesias (7/13), increased hair loss (7/15), vomiting (6/15), pharyngeal injection (6/9), testicular pain (2/9), parotid pain (4/15), rash (3/15), arthritis (3/15) and in two people, meningeal signs. Illness was often biphasic, and was particularly noted to be biphasic in the patients developing meningeal signs; in a number of others, the second phase of illness included more severe headache than previously, as well as problems such as confusion and memory defects. It was noted that a further 32 seropositive individuals had either shown no illness or only very mild illness, not requiring time off work. (J496.58.w1)
    • Radiography: lungs may show changes on radiography. (J83.2.w1)
    • Congenital infection: Following infection in utero, fetal or neonatal death, spontaneous abortion, hydrocephalus or chorioretinitis may occur. (J84.1.w1, J416.232.w1)
      • "Nonobstructive hydrocephalus with periventricular calcifications, chorioretinitis, and psychomotor retardation" were noted in five congenitally infected infants. (J84.1.w1)
      • Both mental and visual defects may occur in neonates with hydrocephalus. (B558.w1)

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Clinical Pathology (Testing Samples incl. Serology)

Overall Clinical Pathology findings
Rodents

Virus and antibodies may be detectable in blood.

  • In Mesocricetus auratus - Golden Hamsters infected as young adults, antibodies were detected by CFT by 10 days post infection, peaked at 60 days and remained detectable, although titres reduced slowly, to at least 210 days. Viraemia was generally cleared by 60 days. (J267.13.w1)
  • In Mesocricetus auratus - Golden Hamster infected as neonates, CF antibody titres peaked at 16 weeks post infection. In individuals which remained healthy, viraemia decreased rapidly from week 12, although virus was still detectable in the urine of some individuals at 59 weeks. In those which developed illness, viraemia increased again from about week 16 and titres of virus in urine also increased to at least week 59; CF antibody titres were lower than in the individuals which remained healthy. Neutralising antibodies were detectable by week 7 in a hamster which cleared infection and remained high to 68 weeks, but in two which developed illness, no or only just-detectable neutralising antibodies developed. (J267.13.w1)
Nonhuman primates

In affected marmosets and tamarins, commonly bilirubin and liver enzymes are elevated; seroconversion may not occur before death. In experimentally infected macaques, viraemia has been detected by three days post inoculation and antibodies by as soon as 13 days; changes in haematological and biochemical parameters did not occur in animals which remained without clinical signs, but raised liver enzymes and bilirubin were reported in those with fatal infection, also variable haematological changes such as thrombocytopaenia and transient leucopaenia followed by leucocytosis.

  • Marmosets: Liver enzymes elevated. (D267.035.w35)(AST = SGOT, GGT, Bilirubin (D267.035.w35, J2.20.w6, J20.284.w1 J100.160.w1)
  • In an outbreak in Leontopithecus rosalia - Golden lion tamarins, blood samples from two individuals revealed slightly increased WBC count and decreased platelets. (P1.1982.w3)
  • Tamarins: in individuals with a longer clinical course of disease, icterus and elevated liver enzymes. (J2.20.w6)
  • In two Saguinus fuscicollis - Saddleback tamarins from a group in which two of five died, aspartate aminotransferase (AST = SGOT) was elevated up to 2,695 U/L but after six weeks had returned to normal levels of 60 - 200 U/L. (J2.20.w6)
  • In Callithrix jacchus - Common marmoset following experimental inoculation, raised aspartate aminotransferase: detectable rise (from normal 60-200 U/L) by four to seven days and rising to 2,000 units/L or higher by 8-9 days post inoculation. Also raised serum bilirubin (reaching 3 mg/dL in one animal by day seven, and rising in the other two, from the normal range of 0 - 0.76 mg/dL). (J100.160.w1)
  • Two Leontopithecus rosalia - Golden lion tamarin at Chafee Zoological Park, California, 1995, did not seroconvert before death. (P1.1996.w8)
  • In a Callimico goeldii - Goeldi's monkey in Dortmund Zoo, Germany, raised aspartate aminotransferase, gamma-glutamyl transferase (9.3 times upper normal value), bilirubin (107 times upper normal value) and creatinine (103 times upper normal value). (J20.284.w1)
  • In Colobus guereza - Black and white colobus (Cercopithecidae - Old-world monkeys (Family)) in the UK, June 2006, blood samples showed active infection. (P3.2007b.w1)
  • In cynomolgus monkeys (Macaca fascicularis - Crab-eating macaque) following experimental subcutaneous inoculation with LCMV-WE strain, raised SGOT and creatine phosphokinase, transient leucopaenia (mainly lymphopaenia) by day seven post infection, then leucocytosis, mainly neutrophils. Fibrin degradation products detectable in blood by day 13 post infection. Viraemia from three days post infection (reaching 5 log10 pfu/mL by day 7 and 7-8 log10 pfu/mL by the time of death) and virus detected in urine (3 to > 6 log10 pfu/mL) from day six onwards. (J214.134.w1)
  • In cynomolgus monkeys (Macaca fascicularis - Crab-eating macaque) following experimental inoculation with LCMV-ARM strain, which did not cause any clinical signs, haematological parameters and serum biochemistry remained normal. Antibodies were detected by IFA by day 13 post inoculation, increasing to titres of 1280-2560 by day 24; neutralizing antibodies were first detectable by plaque reduction test at 35-50 days and titres continued increasing for at least 90 days. (J214.134.w1)
  • In Macaca mulatta - Rhesus macaques experimentally infected: (J71.149.w1)
    • Following intravenous inoculation with LCMV-WE strain, significantly elevated aminotransferases, AO, GGTP and bilirubin (associated with hepatocellular necrosis and cholestasis) on the day of death, as well as greatly reduced plasma albumin (down to < 2.25 g/dL). (J71.149.w1)
      • IL-6 and soluble tumour necrosis factor receptors in plasma were raised following detection of virus in blood; their levels in plasma increased rapidly during the incubation period for the disease. (J71.149.w1)
      • Thrombocytopaenia developed. (J71.149.w1)
      • Liver biopsy samples stained positive for Ki-67 antigen, a marker of proliferation. (J80.77.w5)
    • Following gastric inoculation with LCMV-WE strain, in one individual which developed clinical signs, reduction (two-fold) in plasma albumin by week four post infection, returning to normal in two months. Elevation of plasma ALT, AST, GGTP, AP and bilirubin from day 28-42 post infection, returning to normal in about 2-3 weeks. In the second individual (which did not develop clinical signs of illness), biochemical tests indicating liver function remained mainly within normal ranges. (J71.149.w1)
      • The individual which developed disease and viraemia also showed elevated IL-6 and soluble tumour necrosis factor receptors (sTNFRI and TNFRII); these were raised in parallel with viraemia, peaking at 4-5 weeks. (J71.149.w1)
      • Liver biopsy samples from the individual with transient illness stained positive for Ki-67 antigen, a marker of proliferation. (J80.77.w5)
      • The individual which which developed transient disease and viraemia also developed neutralizing antibodies. (J80.77.w5)
    • Following gastric or intravenous inoculation with LCMV-ARM strain (no clinical signs), biochemical tests indicating liver function remained mainly within normal ranges. (J71.149.w1)
Humans

In humans, the wbc count may be normal or low and thrombocytopaenia may be detected, with antibodies detectable within a few days using IFA test; complement-fixation and neutralising antibodies are detectable later. Virus may occasionally be isolated from serum or blood. In individuals with signs of meningitis, the CSF generally shows reduced glucose, elevated protein, a high lymphocyte count and lymphocytic pleocytosis; virus may be isolated from the CSF.

  • Haematology: WBC count normal or low; sometimes atypical lymphocytes detected, but differential wbc count usually normal. (J421.36.w1)
  • During an outbreak in 15 members of staff at a university hospital, leukopaenia and thrombocytopaenia were noted in the first phase of illness (J496.58.w1)
  • Complement-fixing and neutralizing antibodies develop during illness or during convalescence. (J83.2.w1)
  • CF antibodies are detected for a few months after infection. (J323.66.w1)
  • Neutralizing antibodies may be detected starting 1-2 months after infection and persisting for 2-3 years. (J323.66.w1)
  • IFA can detect infection within a few days of the onset of clinical signs; titres decline after several months but may be detected even three years post infection. (J323.66.w1)
  • During an outbreak in 15 members of staff at a university hospital, all six affected individuals tested were seronegative by IFA in an acute serum sample (taken 4-11 days after the onset of clinical illness) but all 15 were seropositive in convalescent samples taken at 16-653 days after onset. (J496.58.w1)
  • During an outbreak in 15 members of staff at a university hospital, virus was isolated from the serum of one individual and from the serum and CSF of an individual with meningeal signs. (J496.58.w1)
  • CSF
    • Reduced glucose concentration and a high lymphocyte count. (J83.2.w1)
    • Low glucose (sometimes as low as 22 g/dL), elevated protein and lymphocytic pleocytosis. (J421.36.w1)
    • A high lymphocyte count has been noted in several individuals with meningitis. (J216.96.w1)
    • In humans, haematological findings may be unremarkable. (J416.232.w1) Lumbar puncture may reveal lowered cerebrospinal fluid glucose, raised protein and pleocytosis, predominantly mononuclear cells. (J416.232.w1)
    • Virus has been isolated from CSF of several individuals with meningitis. (J216.96.w1)

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Pathological Findings (by anatomical system)

Notes
GROSS PATHOLOGY
Nonhuman primates

In marmosets and tamarins, commonly jaundice, subcutaneous and intramuscular haemorrhages, pleural and pericardial  effusions (sometimes sanguineous), hepatomegaly and splenomegaly; the liver may be golden/yellow tan in colour. In macaques with fatal infection, pleural and pericardial effusion, dark red mottling of the lungs, with consolidation noted in one study; yellowing of the liver was reported in one study and in another, petechiae on the mucosal surface or some organs (urinary bladder, stomach).

  • Marmoset: jaundice, pleural and pericardial effusions (sometimes sanguineous), subcutaneous and intramuscular haemorrhages, hepatomegaly and splenomegaly. (J80.65.w1)
  • Marmosets: hepatitis, lymphadenopathy, pulmonary oedema. (D267.035.w35)
  • In an outbreak in a zoo involving Callimico goeldii - Goeldi's monkey, Callithrix argentata melanura (Callithrix argentata - Silvery marmoset), and Saguinus oedipus - Cotton-top tamarins (J83.16.w1)
    • Excessive pale straw-coloured peritoneal fluid.
    • Excessive pale straw-coloured pericardial fluid (one).
    • Blood-stained pleural effusion.
    • Lungs congested and with patchy collapse in some individuals
    • Hepatic: slightly swollen liver, with mottled pale areas on the surface and on the cut surface.
      • No hepatic abnormality visible in one individual.
  • In an outbreak in Leontopithecus rosalia - Golden lion tamarins (data from seven animals): (P1.1982.w3)
    • Skin: Subcutaneous haemorrhage
    • General: pericardial, thoracid and abdominal transudates (amber, clear, fibrinous, with low cellularity).
    • Pulmonary: pulmonary congestion
    • Hepatic: livers golden, slightly friable, and nutmeg-patterned
    • Adipose: fat deposits reduced
    • GIT: Duodenum: petechiation of the mucosa in one individual. 
  • In outbreaks in Leontopithecus rosalia - Golden lion tamarins from three groups in two years in one zoo, all of two groups of three animals and three of four of another group were affected. (J2.20.w6)
    • General:
      • jaundice
      • subcutaneous and intramuscular haemorrhages
      • pleuro-pericardial effusions, sometimes sanguineous.
    • Hepatic: hepatomegaly.
    • Splenic: splenomegally
  • In Callithrix jacchus - Common marmoset following experimental inoculation. (J100.160.w1)
    • Jaundice in two of three individuals.
    • Liver enlarged and yellow tan in colour in all three individuals.

    (J100.160.w1)

  • In a Callimico goeldii - Goeldi's monkey and three Callithrix pygmaea - Pygmy marmosets in Germany: (J20.284.w1)
    • Jaundice.
    • Hepatic: hepatomegaly.
    • Spleen and lymph nodes: enlarged
    • Pulmonary: pulmonary oedema.

    (J20.284.w1)

  • In cynomolgus monkeys (Macaca fascicularis - Crab-eating macaque) following experimental subcutaneous inoculation with LCMV WE: (J214.134.w1)
    • Hepatic: liver pale yellow. 
    • Spleen: markedly congested.
    • Pulmonary: lungs mottled dark red.
    • Body cavities: thoracic cavity contained large quantities straw-coloured fluid.
    • Cardiac: pericardial sac contained large quantities straw-coloured fluid.
  • In Macaca mulatta - Rhesus macaques following intragastric inoculation with LCMV ME, no significant lesions. (J117.67.w1)
  • In Macaca mulatta - Rhesus macaques following intravenous inoculation with LCMV WE: (J117.67.w1)
    • General: dehydration, thin body condition.
    • Areas of haemorrhage e.g. on the head and around venipuncture sites.
    • Pulmonary: lungs mottled dark and light red; "could be infused with formalin only under moderate pressure.".
    • Lymph nodes: enlargement of inguinal and axillary nodes in one of two individuals.
    • Urinary: mild scattered petechiae on the mucosal surface of the bladder.
    • GIT: stomach mucosa had moderate petechiae in one of two individuals; in the other, there was diffuse transmural reddening of the small intestines, particularly distally.
    • Bone marrow: in the femur, scant, dark red-yellow.

    (J117.67.w1)

Humans:
  • Hydrocephalus, meningitis, chorioretinitis. (D267.035.w35)
  • In an individual with fatal infection: (J106.23.w1)
    • Pulmonary: lungs congested with diminished crepitation, bronchi contained thick yellow fluid
    • CNS: Cerebral and spinal cord vascular congestion; the posterior two thirds of the cerebral hemispheres showed marked softening as well as vascular congestion. (J106.23.w1)
Rodents
  • In mice: (B558.w1)
    • Lymph nodes: may be swollen. Cortex may develop small pale foci. (B558.w1)
    • Spleen: around the central artery, may develop small pale foci. (B558.w1)
    • Lymph nodes, thymus and spleen may have reduced mass (due to lymphoid cell depletion). (B558.w1)
  • In rats:
    • CNS: cerebral hypoplasia. (B558.w1)
HISTOPATHOLOGY
  • Mainly hepatic: diffuse hepatocellular necrosis, formation of acidophilic bodies, and a mild inflammatory infiltrate. (J80.65.w1)
  • Marmosets: multifocal necrosis of hepatocytes, presence of acidophilic inclusion bodies. (D267.035.w35)
  • In an outbreak in a zoo involving Callimico goeldii - Goeldi's monkey, Callithrix argentata melanura (Callithrix argentata - Silvery marmoset), and Saguinus oedipus - Cotton-top tamarins: (J83.16.w1)
    • Hepatic: Variable severity. (J83.16.w1)
      • Mild: hepatocyte size variation, occasional mitotic figures, scattered necrotic hepatocytes, fatty change (mild to moderate) and periportal infiltration of lymphocytes and macrophages, sometimes with infiltration into lobules.
      • Severe: lobular disarray, marked anisocytosis and anisokaryosis, usually plentiful mitoses. Spotty necrosis of hepatocytes, of single cells or cell clusters, with lymphocyte and macrophage infiltration in larger areas of necrosis. In the lobules and around portal tracts and central veins, inflammatory cell infiltrate - lymphocytes, macrophages and occasional polymorphonuclear leucocytes. in most individuals, ballooning of liver cells. in some individuals, lipofuscin in Kupffer cells and macrophages.
  • In an outbreak in Leontopithecus rosalia - Golden lion tamarins (data from seven animals): (P1.1982.w3)
    • Pulmonary: Mild congestion of the lungs, alveolar macrophages ans perivascular lymphocytes noted.
    • Hepatic: marked to moderate hepatocellular necrosis, cellular infiltration with neutrophils, lymphocytes and macrophages, eosinophilic cytoplasmic inclusion bodies in two individuals, and Councilman-like eosinophilic inclusion bodies in one individual. 
    • Thymus, spleen and lymph nodes: necrosis, lymphocyte depletion, haemorrhage, oedema and reticuloendothelial hyperplasia.
    • Renal: Infiltration of the kidney with interstitial and perivascular lymphoplasmacytic cells and macrophages. 
    • Cardiac: Infiltration of the heart with interstitial and perivascular lymphoplasmacytic cells and macrophages. 
    • CNS: Infiltration of the brain with interstitial and perivascular lymphoplasmacytic cells and macrophages.
  • In outbreaks in Leontopithecus rosalia - Golden lion tamarins from three groups in two years in one zoo, all of two groups of three animals and three of four of another group were affected. (J2.20.w6)
    • Hepatic: 
      • Hepatocellular necrosis and swelling, a few lymphocytes and neutrophils present in lobules, associated with acidophilic bodeis (degenerated hepatocyte remnants), and often portal phlebitis.
      • Enveloped virus-like prticles detected, 85 -105 nm diameter, in degenerated hepatocytes.
    • Lymph nodes and spleen: necrosis and inflammation observed.
    • Other organs: necrosis and inflammation observed inconsistently.
  • In Callithrix jacchus - Common marmoset following experimental inoculation. (J100.160.w1)
    • Hepatic: hepatocellular swelling and necrosis, inflammation and acidophilic bodies; occasionally these were found within Kupffer's cells.
    • Lymphoid organs: necrosis
    • Large intestines: necrosis of mucosa.
    • Electron microscopy: Enveloped viruslike particles, 85 - 105 nm diameter in the cytoplasm of hepatocytes. 

    (J100.160.w1)

  • In Callithrix pygmaea - Pygmy marmosets at Fort Worth Zoo, 1991. (J100.167.w1)
    • Hepatic: hepatitis, with periportal infiltration of inflammatory calls, and portal vein vasculitis. (J100.167.w1)
    • CNS: Encephalitis, with prominent gliosis. (J100.167.w1)
    • Immunoassay: viral antigen detected in the liver. (J100.167.w1)
  • In Leontopithecus rosalia - Golden lion tamarins at Fort Worth Zoo, 1991. (J100.167.w1)
    • Hepatic: Extensive hepatitis, formation of acidophilic bodies.
    • CNS: meningitis (mild) and vasculitis.
    • Immunoassay: viral antigen detected in the liver.
    • RNA hybridization: strong hybridization of RNA extracted from the livers with a cDNA probe generated from LCMVCH(OKCZI).
  • In experimentally inoculated Callithrix jacchus - Common marmoset and naturally infected Leontopithecus rosalia - Golden lion tamarin and Saguinus imperator - Emperor tamarin: (J45.148.w1)
    • Hepatic: throughout the liver, hepatocellular degeneration and spotty necrosis. Often, a mild mononuclear inflammator cell infiltrate associated with lesions, and a few neutrophils found throughout the liver. Presence of round, acidophilic bodies (Councilman-like) appearing to arise from hepatocytes or from cytoplasmal segments, found free within sinusoids, and sometimes in Kupffer cells; they varied in number between individuals. (J45.148.w1)
      • Immunoperoxidase staining: LCMV antigen detected, in hepatocytes in and around necrotic areas, and in Kupffer cells and in some apparently normal hepatocytes. In two , antigen-positive biliary epithelial cells were noted in portal triads. (J45.148.w1)
    • Spleen and lymph nodes: necrotic foci, mainly in the centres of follicles.
      • Immunoperoxidase staining: LCMV antigen detected in macrophages and intrafollicular reticular cells, and much sparser than in the liver.
    • Adrenal cortex: small foci of necrosis, mainly in the zona fasciculata.
    • GIT: in the intestines, necrotic foci mainly of enterocytes and goblet cells of the colonic crypts. In one Leontopithecus rosalia - Golden lion tamarin, foci of inflammation of the oesophagean squamous epithelium.
    • Pulmonary: No histopathological lesions detected.

      • Immunoperoxidase staining: in alveolar macrophages and in other cells.

    • Renal/urinary: No histopathological lesions detected.

    • Genital: No histopathological lesions detected.

    • CNS: Meningeal infiltrate of lymphocytes, and cerebral mononuclear cell perivasculitis.

      • Immunoperoxidase staining of epithelial cells of the choroid plexus, and of vascular endothelium, but not of any neurons or supporting cells of the neuropil.

    (J45.148.w1)

  • In Callithrix pygmaea - Pygmy marmosets: (J45.148.w1)

    • Hepatic: intense portal mononuclear cell infiltration, extending into portal vessels. Minimal hepatocellular necrosis, and few acidophilic bodies.

      • Immunoperoxidase staining: LCMV antigens in many hepatocytes; in one individual, also in biliary epithelium.

    • Adrenal: minimal degenerative changes.

      • Immunoperoxidase staining: LCMV antigens present.

    • GIT: Lymphocytic gastritis, focal colonic necrosis.

      • Immunoperoxidase staining: LCMV antigens present in affected areas of colon.

    • Pancreas: lymphocytic pancreatitis

      • Immunoperoxidase staining: LCMV antigens present, particularly in areas of acinar degeneration.

    • Pulmonary: extensive interstitial pneumonia

      • Immunoperoxidase staining: LCMV antigens present in alveolar macrophages and in bronchial lining cells.

    • CNS: in 3/5 individuals, encephalitis, including vasculitis and neuropil involvement.

      • Immunoperoxidase staining: LCMV antigens not found in grey or white matter; in one individual, a small amount of staining of the meninges.

    • Renal:

      • Immunoperoxidase staining: LCMV antigens present in glomeruli and in segments of proximate convoluted tubules.

    (J45.148.w1)

  • In a Callimico goeldii - Goeldi's monkey and three Callithrix pygmaea - Pygmy marmosets in Dortmund Zoo, Germany: (J20.284.w1)
    • Hepatic: hepatitis, including multifocal hepatocyte degeneration and necrosis, diffuse fatty change, mild to moderate periportal mononuclear cell infiltrate (and perivascular in the Callimico goeldii - Goeldi's monkey) and the presence of acidophilic bodies (Councilman-like bodies).
    • Spleen & Lymph nodes: Follicular hyperplasia and depletion of germinal centres.
    • CNS: cerebral perivascullitis, meningeal lymphocytic infiltration (mild); in one individual, focal gliosis in the cortex.
    • PCR: LCMV RNA detected in frozen liver, spleen, serum and urine samples by RT-PCR , and by seminested PCR in paraffin-embedded liver and spleen from one Callithrix pygmaea - Pygmy marmoset.

    (J20.284.w1)

  • In cynomolgus monkeys (Macaca fascicularis - Crab-eating macaque) following experimental subcutaneous inoculation with LCMV WE: (J214.134.w1)
    • Direct immunofluorescence staining: "massive concentrations of LCMV antigens" detected in kidney tubules, in the adrenal cortex, in pancreas (acinar cells, in salivary glands (acinar cells), lung, splenic white pulp. In the liver, occasional foci of antigen were noted in hepatocytes. In the brain, antigens were noted clustered around blood vessels. (J214.134.w1)
  • In Macaca mulatta - Rhesus macaques following intragastric inoculation with LCMV ME. (J117.67.w1)
    • Gastritis; spleen and lymphoid tissues activated. N.B. lesions were mild and may have been incidental findings. (J117.67.w1)
    • RT-PCR: LCMV-specific nucleic acids detected faintly in plasma at two to three weeks post inoculation.
  • In Macaca mulatta - Rhesus macaques following intravenous inoculation with LCMV WE: (J117.67.w1)
    • Pulmonary: moderate multifocal perivascular oedema and haemorrhage.
    • Buccal cavity: necrotic foci 
    • Bone marrow: depletion of cells; adipocyte infiltration
    • Thymus: severe diffuse depletion of lobules; only small numbers of lymphocytes found around Hassall's corpuscles. 
    • Hepatic: scattered hepatocellular necrosis, mild to moderate.
    • Lymph nodes: sinus histiocytosis (inguinal and axillary nodes), moderate generalised follicular depletion, also in one individual paracortical lymphoid hyperplasia.
    • GIT: In one individual, stomach mucosa haemorrhage, mild to moderate.
    • Urinary: In one individual, bladder mucosa haemorrhage, mild to moderate, plus submucosal oedema.
    • RT-PCR: LCMV-specific nucleic acids detected.
    • In situ hybridization: LCMV-specific nucleic acids detected.

    (J117.67.w1)

    • Cellular proliferation markers: liver samples stained positive for Ki-67 antigen, a marker of proliferation. (J80.77.w5)
    • In a Macaca mulatta - Rhesus macaque following intragastric inoculation with LCMV Armstrong, viral nucleic acid was detectable in "most tissues" at 72 hours post inoculation. (J117.67.w1)
  • In an individual human with fatal infection: (J106.23.w1)
    • Cardiac: interstitial oedema.
    • Pulmonary: mild pneumonia, pulmonary infiltrate, intraalveolar inflam infiltrate (lymphocytes, mononuclear cells; septal capillaries were engorged with rbc.
    • CNS: "meningoencephalitis with an associated radiculitis and myelitis"; enncephalitis was most marked in the pons and medulla. The meninges showed a prominent perivascular inflammatory response, mainly of lymphocytes and mononuclear cells; there was similar infiltration of the dilated Virchow-Robin spaces of the cortex, particularly in the frontal, parietal and temporal lobes, and of the ependymal lining of the ventricles. In the dorsal medulla and pons, focal inflammatory nodules: severe inflammation, extending from vessels into the parenchyma, and with extravasation of red blood cells. In the pons, focal collections lymphocytes, mononuclear cells and glia. In the spinal cord and associated membranes marked perivascular cuffing was noted and in the nerve roots and spinal ganglia, some lymphocytic infiltration.
    • Direct immunofluorescence of unfixed brain sections resulted in specific fluorescence of meninges and in the cytoplasm of about 15% of cells in the parietal and temporal lobes.

    (J106.23.w1)

  • In mice: (B558.w1)

    • CNS: meninges show lymphocytic inflammatory infiltration; cerebral and cerebellar hypoplasia may occur, also retinopathy.
    • Lymph nodes: foci with relative lymphocyte deficiency, depletion of cells in "thymus dependent areas", foci of haemorrhage, karyorrhexis and coagulation necrosis.

VIRUS ISOLATION

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Diagnostic Criteria

General Indicative Signs

In marmosets and tamarins: 

In humans:

  • The clinical signs of lymphocytic choriomyelitis may be seen with a variety of other viral infections. Severe myalgia in individuals with 'flu-like symptoms may indicate this disease as a possibility. (J416.232.w1), as may 'flu-like illness with leucopaenia and thrombocytopaenia in individuals having contact with rodents. (J496.58.w1)
Definitive Diagnosis Definitive diagnosis may be made by:
  • Virus isolation
    • from blood collected during the acute phase of infection (febrile phase in humans), or possibly during the period of meningitis;
    • from CSF during the period of meningitis;
    • from tissues at autopsy/necropsy.

    (B324.50.w50, B558.w1)

  • Immunohistochemical staining of tissue sections. (J45.148.w1, J222.354.w1)
  • RT-PCR of tissue sections, serum or plasma, or urine. (J20.284.w1)
  • Seroconversion:
    • Fourfold rise in titre in paired acute and convalescent serum samples. (B244.w2)
    • Presence of IgM in a serum sample. (B244.w2)
    • Detection of CF (complement fixing) antibodies (starting in the first week of infection and detectable for a few weeks in humans). (B558.w1)
    • IFA (indirect fluorescent antibody test) - these antibodies are detectable within a week of infection, peaking within a month and persisting for a year or more. (B558.w1)
      • To detect a rise in antibody titre in paired sera, the first serum sample must be collected early in the clinical course of the disease. (B558.w1)
    • Note: neutralising antibodies appear later but remain detectable lifelong, therefore are useful in epidemiological studies but are not particularly useful for diagnosis of clinical cases. (B558.w1)
Similar Diseases
  • In marmosets and tamarins: other causes of hepatitis, including hepatitis A and hepatitis B. (P1.1982.w3, P1.1996.w8)
  • In humans: a variety of other viral infections. (J416.232.w1)
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Treatment and Control

Specific Medical Treatment (Antiserum, Antidote, Anti-(viral/bacterial/fungal) etc.)

Specific Medical Treatment

ANTISERUM

There is no data on the use of antiserum in the treatment of LCMV infection, although passive antibody therapy has been used successfully for the treatment of experimental infection Lassa virus (another arenavirus), in Macaca fascicularis - Crab-eating macaque.

  • It has been suggested that LCMV-immune serum could be used in callitrichids in the face of an outbreak; it is not known whether this treatment would be effective. (J2.24.w7)
  • Passive antibody therapy has been used successfully for the treatment of experimental infection with another arenavirus, Lassa virus, in cynomolgus monkeys (Macaca fascicularis - Crab-eating macaque). Seven of eight monkeys were successfully protected (survived a lethal dose of the virus) following treatment with undiluted serum at 1 mL/kg on days 0, 3 and 6 post virus inoculation . It was noted that early treatment with a high level of neutralizing antibodies, preferably from an individual infected with homologous strain of virus was critical for the treatment to be successful. (J267.44.w1)

ANTIVIRAL DRUGS

Ribavirin has been used in the treatment of both humans and non-human primates.

  • In vitro, LCMV is susceptible to ribavirin. (B244.w2)
  • Ribavirin is effective in the treatment of the arenavirus causing Lassa fever in humans. (B244.w2)
  • Ribavirin was used in the successful treatment of a human transplant patient with LCMV. Initially, ribavirin was given intravenously, with a loading dose of 30 mg/kg body weight followed by 16 mg/kg every six hours for four days, then 8 mg/kg every eight hours , and after clinical stabilisation, orally at 400 mg each morning and 600 mg each evening (immunosuppressive drug treatment was discontinued). (J222.354.w1)
  • It has been suggested that ribavirin could be used in callitrichids in the face of an outbreak; it is not known whether this  treatment would be effective. (J2.24.w7)
  • Ribavirin has been used in tamarins during an outbreak of LCMV. (J100.167.w1)
  • Antiviral therapy was used in a Colobus guereza - Black and white colobus (Cercopithecidae - Old-world monkeys (Family)) in the UK, June 2006, which was showing severe neurological signs. Treatment continued until clinical signs abated and shedding of virus had ceased. (P3.2007b.w1)
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  • No specific techniques described

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General Nursing and Surgical Techniques

Nursing and Supportive Care
  • General supportive care is appropriate. (B244.w2)
  • In individuals receiving immunosuppressive medication, cessation of the immunosuppressive medication may be an important part of treatment. (J222.354.w1)
Surgical Treatment
  • In human infants with congenital LCMV infection, it may be necessary to place a shunt for the treatment of obstructive hydrocephalus causing increased intracranial pressure. (B244.w2)
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Vaccination & Prophylactic Treatment

Vaccination
  • Experimentally, intramuscular injection of a plasmid construct encoding LCMV nucleoprotein (NP) induced both an anti-LCMV antibody response and priming of LCMV-specific cytotoxic T-lymphocytes (CTL). Injection of plasmids encoding nucleoprotein or glycoprotein conferred protection on a proportion of vaccinated mice (about 50%); this protection was dependent on the host's major histocompatibility complex (no protection for BALB/c mice inoculated with plasmid encoding LCMV glycoprotein). It was thought that the induced cytotoxic T lymphocytes were probably responsible for the observed protection. CTL activity was not easily detected in naive mice at four days post inoculation of LCMV, but was easily detectable in some of the plasmid-immunized individuals. (J80.69.w3)
Prophylactic Treatment --
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Environmental and Population Control Measures

General Environment Changes, Cleaning and Disinfection
  • For control of this infection in primates, mice should not be fed to primates as a part of their diet. (J100.167.w1, P1.1996.w8)
  • Enclosures should be designed to minimise access of mice into the enclosure, and safe methods of rodent control should be carried out to minimise wild rodent populations in the vicinity of primate enclosures. (J100.167.w1, P1.1996.w8)
  • The best prevention of LCMV infection is avoidance of contact with infected rodents. (B558.w1)
  • Good sanitation is recommended to avoid infection of humans, with control of mouse infestations. (B282.16.w16)
  • To avoid cross-contamination of rodents:
    • Clean and disinfect (e.g. with bleach) cages, houses and any reusable equipment (water bottles, food dishes etc.) which has been used for infected rodents before placing other rodents in the cage. (N7.54.w3)
    • Wash hands/change gloves after handling rodents before carrying out other activities or handling other groups of rodents. (N7.54.w3)
CLICK THE LINKS FOR Technique Descriptions, if available
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Population Control Measures
  • Colonies of susceptible rodents, particularly mice and hamsters, should be monitored regularly for infection. It is recommended that where a colony (e.g. a laboratory or pet-trade breeding colony) is found to be infected, the whole colony should be destroyed and the premises decontaminated before new, LCMV-free animals are brought in. (B558.w1)
  • In a colony of captive-bred wild mice (Mus musculus - House mouse), following initial detection of LCMV infection during a serosurvey, infected animals were detected using a PCR assay and were eliminated from the colony. (J83.41.w1)
  • Healthy rodents should not be housed in the same room as rodents which are or might be infected. (N7.54.w3)
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Isolation and Quarantine
  • Prevent contact of captive rodents with wild house mice. (N7.54.w3)
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CLICK THE LINKS FOR OVERVIEWS of management techniques available
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Authors & Referees

Authors Debra Bourne MA VetMB PhD MRCVS (V.w5)
Referee Prof. Juan C. de la Torre PhD (V.w168)

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